PubMed Health⌕ Search

Biomedical subjects

Michael Miller

Publications and source records attributed to Michael Miller.

At least 37 records · Page 2Linked to original sources
PubMed2006

Non-alcoholic fatty liver disease in HIV-positive patients predisposes for acute-on-chronic liver failure: two cases.

Non-alcoholic fatty liver disease is a prominent feature in HIV-positive patients. We present two patients with long-lasting HIV-infection who suffered from this disease, as induced by highly active anti-retroviral therapy (HAART). The patients developed acute-on-chronic (AOC) liver failure after either (case 1) acute infection with hepatitis A virus (HAV) or (case 2) methamphetamine abuse ('Ecstasy'). Approximately 1 week after visiting an area endemic for HAV, case 1, a male patient, presented with icterus, elevated liver transaminases and HAV IgM. Previous examinations had demonstrated normal liver transaminase activities while hepatic steatosis had been suspected. He developed complications associated with liver failure including renal failure as well as pleural and pericardial effusions. Case 2, a second male patient, developed both liver failure and lactic acidosis 24 h after methamphetamine abuse. Both patients suffered from fatty liver in the pre-acute stage as indicated by ultrasound examination. After developing symptoms of liver failure, HAART was discontinued in both patients. Follow-up visits demonstrated that the patients recovered clinically with almost normalized laboratory parameters. In HIV infection, HAART-induced hepatopathological alterations may exist despite the absence of relevant laboratory parameters. These patients are likely to develop AOC liver failure when subjected to acute risk factors such as hepatitis viruses and narcotics or other drugs. In patients treated with HAART, we thus highly recommend hepatitis A and B virus vaccinations, and close monitoring of liver parameters.

Acute Disease↗
PubMed2006

Superimposed electrical stimulation: assessment of voluntary activation and perceived discomfort in healthy, moderately active older and younger women and men.

OBJECTIVE: An inability of the nervous system to fully activate the muscle is one factor that can contribute to age-related muscle weakness. Superimposed electrical stimulation can be used to determine voluntary muscle activation (VA). The aim of this study was to assess VA of the quadriceps muscle in healthy older and younger subjects. DESIGN: Electrical stimulation causes moderate discomfort in younger subjects, but no study has assessed discomfort in older subjects. The quadriceps muscle in 20 moderately active older subjects (mean age, 75 yrs) and 12 younger subjects (mean age, 25 yrs) was stimulated during two maximal voluntary contractions using a 100-Hz pulse train. A visual analog scale for pain (VAS-pain) was used to evaluate discomfort. RESULTS: Ability to activate the quadriceps muscle was generally very high, and there was no significant difference between the older (mean, 0.96) and younger (mean, 0.98) subjects. Discomfort did not differ between the older (mean VAS-pain score, 41 mm) and younger (mean VAS-pain score, 37 mm) subjects. CONCLUSIONS: Our results indicate that healthy, moderately active older subjects have the ability to almost complete VA of the quadriceps muscle and that discomfort during electrical stimulation is generally moderate.

Adult↗
PubMed2006

Lead toxicity in a 14-year-old female with retained bullet fragments.

In the past 3 decades, lead levels in North American children have been declining. Despite the decline in lead exposure, lead toxicity remains a significant childhood environmental health hazard. The usual route of lead exposure is through ingestion, but lead toxicity secondary to retained bullet fragments has been well documented in the adult literature. The diagnosis of lead toxicity is often difficult and delayed secondary to vague and transient symptoms. Recognizing high-risk characteristics of bullet fragments can improve clinician awareness to the possibility of lead toxicity. The primary management of patients with continued lead exposure is to remove the source of exposure. However, in the case of retained bullet fragments, initiation of chelation therapy before surgical removal may be essential in preventing systemic toxicity. We present the case of a 14-year-old female with lead toxicity who presented with an 18-month course of chronic abdominal pain, vomiting, and anorexia 2 years after sustaining a gunshot wound to the right leg. The patient was treated with oral succimer and operative removal of bullet fragments.

Adolescent↗
PubMed2006

The role of the phospholipid sphingomyelin in heart disease.

Sphingomyelin (SM) is an integral component of mammalian cell membranes and nerves. However, the inability to catabolize SM may lead to its accumulation in various tissues and organs, resulting in pathological disorders such as Niemann Pick disease. Elevated levels of SM have also been identified as an independent risk factor for coronary heart disease. During the past two decades, data have emerged that support an important role for metabolites of SM, such as ceramide and sphingosine-1-phosphate, in the regulation of phenotypic changes such as cell proliferation, cell-cycle arrest, apoptosis and angiogenesis. Further studies of the molecular and pathobiological basis of these phospholipids may facilitate advances in the discovery of drugs with which to mitigate diseases that may result from an elevation in SM and its metabolites.

Animals↗
PubMed2005

High attributable risk of elevated C-reactive protein level to conventional coronary heart disease risk factors: the Third National Health and Nutrition Examination Survey.

BACKGROUND: C-reactive protein (CRP), a marker of systemic inflammation, is predictive of coronary heart disease (CHD) events. However, the extent to which high CRP levels (>3 mg/L) may be attributable to high cholesterol levels and other CHD risk factors has not been well defined. METHODS: The prevalence of high CRP levels in the third National Health and Nutrition Examination Survey (n = 15 341) was studied using CHD risk-factor cut points designated as abnormal (total cholesterol values, >or=240 mg/dL [>or=6.22 mmol/L]; fasting blood glucose levels, >or=126 mg/dL [>or=6.99 mmol/L]; blood pressure, >or=140/90 mm Hg; body mass index [BMI], >or=30 kg/m(2); high-density lipoprotein cholesterol values, <40 mg/dL [<1.04 mmol/L] for men and <50 mg/dL [<1.30 mmol/L] for women; triglyceride levels, >or=200 mg/dL [>or=2.26 mmol/L]; current smoking status) or borderline (total cholesterol values, 200-239 mg/dL [5.18-6.19 mmol/L]; fasting blood glucose levels, 100-125 mg/dL [5.55-6.94 mmol/L]; blood pressure, 120-139/80-89 mm Hg; BMI, 25.0-29.9 kg/m(2), and triglyceride values 150-199 mg/dL [1.70-2.25 mmol/L], former smoking status), or normal. RESULTS: Weighted multiple logistic regression analysis demonstrated that high CRP level was significantly more common with obesity (odds ratio [OR], 3.78; 95% confidence interval [CI], 3.28-4.35]), overweight (OR, 1.88; 95% CI, 1.62-2.18), and diabetes (OR, 1.91; 95% CI, 1.54-2.38) and that high CRP level was rare in the absence of any borderline or abnormal CHD risk factor in men (4.4%) and women (10.3%). Overall, the risk of elevated CRP level attributable to the presence of any abnormal or borderline CHD risk factor was 78% in men and 67% women. CONCLUSIONS: These data suggest that elevated CRP levels in the general population are in large measure attributable to traditional CHD risk factors. Moreover, CRP level elevation is rare in the absence of borderline or abnormal risk factors. As such, CRP measurements may have limited clinical utility as a screening tool beyond other known CHD risk factors.

Adolescent↗
PubMed2005

Synthesis and evaluation of CCR5 antagonists containing modified 4-piperidinyl-2-phenyl-1-(phenylsulfonylamino)-butane.

Synthesis of analogs containing more rigid bicyclic piperidine replacements for the 4-benzyloxycarbonyl-(ethyl)amino-piperidine moiety of the CCR5 antagonist structure, 1, is described. Although similar binding affinity to the lead was achieved with some analogs they were overall less potent anti-HIV agents suggesting that other features besides CCR5 binding are required for good anti-viral activity.

Anti-HIV Agents↗
PubMed2005

Semi-automated basal ganglia segmentation using large deformation diffeomorphic metric mapping.

This paper investigates the techniques required to produce accurate and reliable segmentations via grayscale image matching. Finding a large deformation, dense, non-rigid transformation from a template image to a target image allows us to map a template segmentation to the target image space, and therefore compute the target image segmentation and labeling. We outline a semi-automated procedure involving landmark and image intensity-based matching via the large deformation diffeomorphic mapping metric (LDDMM) algorithm. Our method is applied specifically to the segmentation of the caudate nucleus in pre- and post-symptomatic Huntington's Disease (HD) patients. Our accuracy is compared against gold-standard manual segmentations and various automated segmentation tools through the use of several error metrics.

Algorithms↗
PubMed2005

Angiographic diagnosis and endovascular management of nonvariceal gastrointestinal hemorrhage.

Diagnostic angiography still plays an essential role in the diagnosis of patients,particularly those with acute lower GI bleeding. Transcatheter therapy appears to be a viable treatment alternative in selected patients with GI bleeding. Many interventionists today believe embolotherapy to be more effective initially and to have better long-term results, specifically less rebleeding, than vasopressin infusion with at least equal complication rates. Unfortunately, direct comparison of the two techniques in a randomized, controlled fashion has not been performed. Small patient series, such as those summarized here, suggest that the results of the two techniques are essentially equal, and ischemic complications appear more prevalent with embolotherapy. The use of embolotherapy--either empirically based on endoscopic or surgical findings or directed against a site found to have contrast extravasation-represents the current intervention of choice in the case of upper GI bleeding refractory to endoscopic intervention. Head-to-head studies directly comparing the efficacy, morbidity, and mortality associated with endovascular or surgical correction of bleeding from the upper GI tract is needed. Although the current tide favors embolotherapy in the lower GI tract, infusion of vasoconstricting agents deserves more attention. To that end, there is a great need for scientific data regarding the safety and efficacy of transcatheter therapy for upper and lower GI bleeding.

Angiography↗
PubMed2005

Chromosomal localization of two antihemostatic salivary factors in Simulium vittatum (Diptera: Simuliidae).

The chromosomal locations of two genes encoding the salivary protein products Simulidin (SVAT) and Simulium vittatum erythyma protein (SVEP) were identified using high-resolution cytogenetic mapping. Chromosomal subsection levels were determined from larval and adult salivary gland polytene chromosomes and adult Malphigian tubule chromosomes. Syntenic relationships occurred for both loci from a wild population of Simulium vittatum IIIL-1 collected in central Alabama and the colonized IS-7 S. vittatum sibling. cSVAT mapped to the short arm of chromosomes III, IIIS-72a4.5 and cSVEP mapped to the long arm of chromosome III, IIIL-96b1. cSVAT sits proximal to a common IIIS-2 paracentric inversion, which occurs predominately as the standard sequence in the IIIL-1 sibling and as the inverted sequence in the IS-7 sibling. cSVEP sits close to the differentiated X chromosomes in the IIIL-1 sibling.

Alabama↗
PubMed2005

High prevalence of C-reactive protein elevation with normal triglycerides (100-149 mg/dL): are triglyceride levels below 100 mg/dL more optimal in coronary heart disease risk assessment?

BACKGROUND: The National Cholesterol Education Program defines a fasting triglyceride level below 150 mg/dL as normal. However, observational data suggest that triglyceride levels above 100 mg/dL may predict coronary heart disease (CHD) events. METHODS: To determine the prevalence of systemic inflammation with a normal triglyceride level (100-149 mg/dL), data obtained from the population-based cross-sectional study of 4412 men and women in the third National Health and Nutrition Examination Survey were reviewed. Measurements included fasting lipids and lipoproteins and serum C-reactive protein (CRP) level measured using a Behring Nephelometer Analyzer System. RESULTS: High CRP level was equally prevalent whether the designated triglyceride cutpoint was greater than or equal to 100 (unadjusted OR, 2.0; 95% CI, 1.7-2.3) or greater than or equal to 150 (unadjusted OR, 1.9; 95% CI, 1.6-2.2). After adjustment for other covariates, the triglyceride range of 100 to 149 mg/dL remained independently associated with elevated CRP level (OR, 1.3; 95% CI, 1.02-1.67). In addition, an approximately fivefold higher likelihood of elevated CRP level was observed with triglyceride levels between 100 and 149 mg/dL and normal body mass index (BMI; 24-24.9) compared with lower triglyceride level (<65 mg/dL) and BMI (<22) (P < 0.0001). CONCLUSIONS: These data indicate that "normal" triglyceride levels (100-150 mg/dL) are associated with systemic inflammation and that lower fasting triglyceride levels (eg, <100 rather than <150 mg/dL) may be a more optimal cutpoint in CHD risk assessment.

Adult↗
PubMed2005

Outcome after orthotopic liver transplantation in five HIV-infected patients with virus hepatitis-induced cirrhosis.

BACKGROUND: We report on our experiences with orthotopic liver transplantation (OLT) in HIV-infected patients. Between July 1998 and October 2001, five HIV-infected patients underwent OLT because of virus-induced liver cirrhosis. One patient suffered from hepatitis B virus (HBV)-, three patients from hepatitis C virus (HCV)- and one patient from HCV/HBV/HDV-related cirrhosis (HDV, hepatitis D virus). The mean duration of HIV infection was 15 years. Patients were prospectively followed up with a mean duration of 25.6 months. RESULTS: Three patients died 3, 10 and 31 months after OLT, respectively, due to graft failure. The causes of graft failure were: recurrent thrombosis of the hepatic artery, HCV-associated cholestatic hepatitis and chemotherapy-induced liver damage due to Hodgkin's disease, which was diagnosed 17 months after OLT, in addition to chronic HCV disease. The two survivors show a stable liver function and non-progredient HIV infection under antiretroviral therapy 61 and 23 months after OLT, respectively. CONCLUSIONS: A medium- or even long-term survival after OLT can be achieved in HIV-infected patients without progression of HIV disease under antiretroviral therapy. However, in our study three out of five patients died due to graft failure. Therefore, prognostic criteria have to be defined for the selection of HIV-infected patients, who may benefit from OLT.

Adult↗
PubMed2005

Comparative selection of the K65R and M184V/I mutations in human immunodeficiency virus type 1-infected patients enrolled in a trial of first-line triple-nucleoside analog therapy (Tonus IMEA 021).

Tonus was a pilot study in which previously untreated human immunodeficiency virus type 1 (HIV-1)-infected patients received the combination of abacavir, lamivudine, and tenofovir once a day. There was a high rate of early virological failure, and the M184V and K65R mutations were frequently detected at week 12 (W12). The objective of this study was to examine the selection dynamics of the K65R and M184V/I mutations. Bulk sequencing of the reverse transcriptase (RT) gene was performed on plasma HIV-1 RNA at baseline, W4, and W12 for 21 patients with detectable viral loads. The RT genes from baseline, W4, and W12 plasma samples from five patients who developed both M184V and K65R but with different mutational patterns were also cloned and screened for the K65R mutation by selective real-time PCR. At baseline, bulk sequencing and clonal analysis showed only wild-type RT sequences. At W4, M184V/I was detected in 12/19 patients and K65K/R in 2 patients by bulk sequencing. At W12, M184V/I was found in 18/20 patient, together with the K65R in 13 patients. At W4, clonal analysis revealed the K65R mutation in 0.6 to 48% of clones in the five patients studied. At W12, the K65R mutation was found in 30 to 100% of clones. K65R and M184V/I seemed to arise in separate clones, followed by an enrichment of viruses containing both mutations. The clinical relevance of this independent evolution is unclear. M184V/I was selected more frequently than K65R at W4. However, K65R was also detected early using a clone-sensitive genotyping method. All three nucleoside analogs are known to select the K65R and/or M184V/I mutation. This convergent genetic pathway to resistance, associated with lower antiretroviral potency, may explain the high selection rate of these mutations in this trial.

Adenine↗
PubMed2005

A novel assay allows genotyping of the latent reservoir for human immunodeficiency virus type 1 in the resting CD4+ T cells of viremic patients.

A latent reservoir for human immunodeficiency virus type 1 (HIV-1) consisting of integrated provirus in resting memory CD4+ T cells prevents viral eradication in patients on highly active antiretroviral therapy (HAART). It is difficult to analyze the nature and dynamics of this reservoir in untreated patients and in patients failing therapy, because it is obscured by an excess of unintegrated viral DNA that constitutes the majority of viral species in resting CD4+ T cells from viremic patients. Therefore, we developed a novel culture assay that stimulates virus production from latent, integrated HIV-1 in resting CD4+ T cells in the presence of antiretroviral drugs that prevent the replication of unintegrated virus. Following activation, resting CD4+ T cells with integrated HIV-1 DNA produced virus particles for several days, with peak production at day 5. Using this assay, HIV-1 pol sequences from the resting CD4+ T cells of viremic patients were found to be genetically distinct from contemporaneous plasma virus. Despite the predominance of a relatively homogeneous population of drug-resistant viruses in the plasma of patients failing HAART, resting CD4+ T cells harbored a diverse array of wild-type and archival drug-resistant viruses that were less fit than plasma virus in the context of current therapy. These results provide the first direct evidence that resting CD4+ T cells serve as a stable reservoir for HIV-1 even in the setting of high levels of viremia. The ability to analyze archival species in viremic patients may have clinical utility in detecting drug-resistant variants not present in the plasma.

Anti-HIV Agents↗
PubMed2005

Cross-resistance testing of next-generation nucleoside and nucleotide analogues against lamivudine-resistant HBV.

Several next-generation nucleoside and nucleotide analogues are currently in clinical development for the treatment of chronic hepatitis B. However, the efficacy of newer agents against lamivudine-resistant hepatitis B virus (HBV) has not been fully explored. To investigate this in vitro, we generated novel stable cell lines expressing HBV encoding the four major patterns of lamivudine resistance mutations (rtL180M+rtM204V, rtV173L+rtL180M+rtM204V, rtM204I and rtL180M+ rtM204I). Using these cell lines, we assessed the susceptibility of all four strains of lamivudine-resistant HBV to eleven nucleoside analogues in various stages of clinical development. Our studies indicate that lamivudine-resistant HBV remain sensitive to acyclic phosphonate nucleotides (adefovir, tenofovir, and alamifovir), have reduced susceptibility to entecavir, and have high-level cross-resistance to all L-nucleosides tested including emtricitabine, telbivudine, clevudine, and torcitabine.

Cell Line, Tumor↗